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1
Júnior, Sérgio Robson Martucci, Moyses Isaac Cohen, Renato Andrade Chaves, Marco Aurélio Fernandes Teixeira, Richam Faissal El Hossain Ellakkis, Lucas Crociati Meguins, and Dionei Freitas De Morais. "Unusual Penetrating Cranioencephalic Injury by a Harpoon in a Brazilian Man." JBNC - JORNAL BRASILEIRO DE NEUROCIRURGIA 23, no. 4 (March 29, 2018): 342–45. http://dx.doi.org/10.22290/jbnc.v23i4.1233.
Повний текст джерелаАнотація:
Penetrating brain injury due to low energy objects is an unusual cause of head trauma, unlike gunshot wounds. Most cases reported are noteworthy due to its large dimension and, sometimes, good functional outcome. The present report describes the case of a Brazilian man presenting with a deep penetrating brain injury by a harpoon and no neurologic deficits. We discuss the main mechanisms of trauma and make a brief review of the literature upon epidemiological aspects and possible therapeutic approach. The early and appropriate neurosurgical management, on experience hands, may improve considerably patient outcome.
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Chang, Yuan-Pin, Ming-Kai Hsiao, Dean-Kuo Liu, and King-Chuen Lin. "Rotational and vibrational state distributions of NaH in the reactions of Na(4S2,3D2,and6S2) with H2: Insertion versus harpoon-type mechanisms." Journal of Chemical Physics 128, no. 23 (June 21, 2008): 234309. http://dx.doi.org/10.1063/1.2939570.
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Rodríguez-Mayorga, Mauricio, Eloy Ramos-Cordoba, Pedro Salvador, Miquel Solà, and Eduard Matito. "Bonding description of the Harpoon mechanism." Molecular Physics 114, no. 7-8 (December 16, 2015): 1345–55. http://dx.doi.org/10.1080/00268976.2015.1121297.
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Parent, André. "Duchenne De Boulogne: A Pioneer in Neurology and Medical Photography." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 32, no. 3 (August 2005): 369–77. http://dx.doi.org/10.1017/s0317167100004315.
Повний текст джерелаАнотація:
ABSTRACT:Guillaume-Benjamin-Amand Duchenne was born 200 years ago in Boulogne-sur-Mer (Pas-de-Calais, France). He studied medicine in Paris and became a physician in 1831. He practiced general medicine in his native town for about 11 years and then returned to Paris to initiate pioneering studies on electrical stimulation of muscles. Duchenne used electricity not only as a therapeutic agent, as it was commonly the case earlier in the 19th century, but chiefly as a physiological investigation tool to study the anatomy of the living body. Without formal appointment he visited hospital wards across Paris searching for rare cases of neuromuscular disorders. He built a portable electrical device that he used to functionally map all bodily muscles and to study their coordinating action in health and disease. He gave accurate descriptions of many neuromuscular disorders, including pseudohypertrophic muscular dystrophy to which his name is still attached (Duchenne muscular dystrophy). He also invented a needle system (Duchenne's histological harpoon) for percutaneous sampling of muscular tissue without anesthesia, a forerunner of today's biopsy. Duchenne summarized his work in two major treatises entitled De l'électrisation localisée (1855) and Physiologie des mouvements (1867). Duchenne's iconographic work stands at the crossroads of three major discoveries of the 19th century: electricity, physiology and photography. This is best exemplified by his investigation of the mechanisms of human physiognomy in which he used localized faradic stimulation to reproduce various forms of human facial expression. The album that complements his book on this issue is considered a true incunabulum of photography. Duchenne de Boulogne, a shy but hard-working, acute and ingenious observer, became one of most original clinicians of the 19th century. He died in Paris in 1875.
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Lee, Taegon, Jooyoung Kim, Jaeheung Park, Youngshang Pak, Hyojoon Kim, and Manho Lim. "Rebinding dynamics of NO to microperoxidase-8 probed by time-resolved vibrational spectroscopy." Physical Chemistry Chemical Physics 18, no. 7 (2016): 5192–202. http://dx.doi.org/10.1039/c5cp06336a.
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Hoshino, Shoma, Yukio Nakano, Mitsunori Araki, Takashi Ishiwata, and Koichi Tsukiyama. "Collision induced state-to-state energy transfer dynamics between the 2u (1D2) and 2g (1D2) ion-pair states of I2." Physical Chemistry Chemical Physics 18, no. 21 (2016): 14292–98. http://dx.doi.org/10.1039/c6cp00222f.
Повний текст джерелаАнотація:
The collision induced state-to-state energy transfer between the 2u (1D2) and 2g (1D2) ion-pair states of I2 could be explained by the harpoon mechanism.
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Luo, Zhixun, Cüneyt Berkdemir, Jordan C. Smith, and A. W. Castleman. "Cluster reaction of [Ag8]−/[Cu8]− with chlorine: Evidence for the harpoon mechanism?" Chemical Physics Letters 582 (September 2013): 24–30. http://dx.doi.org/10.1016/j.cplett.2013.07.029.
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Gordon, Evgenii B., V. G. Egorov, V. T. Mikhkel'soo, S. E. Nalivaĭko, V. S. Pavlenko, V. É. Peét, and A. B. Treshchalov. "Harpoon mechanism of formation of excimer molecules in an electric-discharge XeCl laser." Soviet Journal of Quantum Electronics 18, no. 2 (February 28, 1988): 180–82. http://dx.doi.org/10.1070/qe1988v018n02abeh011468.
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Luo, Yangyang, Qingyang Wang, Ru Bai, Ruixiang Li, Lu Chen, Yifan Xu, Ming Zhang, and Dong Duan. "The Effect of Transcription Factor MYB14 on Defense Mechanisms in Vitis quinquangularis-Pingyi." International Journal of Molecular Sciences 21, no. 3 (January 21, 2020): 706. http://dx.doi.org/10.3390/ijms21030706.
Повний текст джерелаАнотація:
In the current study, we identified a transcription factor, MYB14, from Chinese wild grape, Vitis quinquangularis-Pingyi (V. quinquangularis-PY), which could enhance the main stilbene contents and expression of stilbene biosynthesis genes (StSy/RS) by overexpression of VqMYB14. The promoter of VqMYB14 (pVqMYB14) was shown to be induced as part of both basal immunity (also called pathogen-associated molecular pattern (PAMP)-triggered immunity, PTI) and effector-triggered immunity (ETI), triggered by the elicitors flg22 and harpin, respectively. This was demonstrated by expression of pVqMYB14 in Nicotiana benthamiana and Vitis. We identified sequence differences, notably an 11 bp segment in pVqMYB14 that is important for the PTI/ETI, and particularly for the harpin-induced ETI response. In addition, we showed that activation of the MYB14 promoter correlates with differences in the expression of MYB14 and stilbene pattern induced by flg22 and harpin. An experimental model of upstream signaling in V. quinquangularis-PY is presented, where early defense responses triggered by flg22 and harpin partially overlap, but where the timing and levels differ. This translates into a qualitative difference with respect to patterns of stilbene accumulation.
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Hijas-Gómez, Ana Isabel, Mar Polo-DeSantos, Setefilla Luengo-Matos, and Luis María Sánchez-Gómez. "PP107 Harpoon™: A Novel Device For Transapical Mitral Valve Repair." International Journal of Technology Assessment in Health Care 35, S1 (2019): 57–58. http://dx.doi.org/10.1017/s026646231900237x.
Повний текст джерелаАнотація:
IntroductionMitral regurgitation (MR) is the most prevalent heart valve condition in Western countries. Open-heart mitral valve reconstruction is the conventional surgical treatment for MR, whereby the valve's cords are replaced with expanded polytetrafluoroethylene cords. Novel devices have introduced minimally invasive alternatives, such as transapical beating-heart valve repair. Among these alternatives, the Harpoon™ Mitral Valve Repair System (Edwards Lifesciences LLC) may have potential advantages (a smaller diameter valve introducer to minimize bleeding and a different anchoring mechanism). This study aimed to assess the efficacy and safety of Harpoon in minimally invasive mitral valve surgery.MethodsAn early assessment of the technology was conducted by reviewing relevant literature from the following databases: PubMed, EMBASE, Web of Science, the Trip Database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, the Cochrane Library, and the Centre for Reviews and Dissemination. Relevant clinical studies published up to 30 January 2018 were included.ResultsOnly two publications, by the same research group, were included: an observational study of 11 patients and the prospective, nonrandomized TRACER trial (n = 30). During the procedure, MR was reduced from severe to none in 73 to 86 percent of patients and severe to mild in 14 to 27 percent. At one month, MR was rated as mild or lower in 82 to 89 percent of patients. At six months, MR had worsened to moderate or severe in 16 percent of patients from the TRACER trial. Safety issues within 30 days (18% to 27% of patients) included intraoperative conversion to open surgery, reoperation, pleural effusion, hemopericardium, and atrial fibrillation. There were no intra- or postoperative deaths.ConclusionsCurrent evidence on the Harpoon device is scarce. Although published studies showed improvement in MR in most patients, there are still issues regarding safety, lack of long-term results, comparability with other procedures, and costs. While promising, further research is required before recommending routine use of this technology.
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Liu, Dean-Kuo, and King-Chuen Lin. "Reaction dynamics of Mg(3 1P1, 4 1S0) with H2: insertion versus harpoon mechanism." Chemical Physics Letters 274, no. 1-3 (August 1997): 37–40. http://dx.doi.org/10.1016/s0009-2614(97)00635-0.
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Mo, Wenwei, Paul D. Walker, Yang Tian, and Nong Zhang. "Dynamic analysis of unilateral harpoon-shift synchronizer for electric vehicles." Mechanism and Machine Theory 157 (March 2021): 104173. http://dx.doi.org/10.1016/j.mechmachtheory.2020.104173.
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Mo, Wenwei, Paul D. Walker, and Nong Zhang. "Dynamic analysis and control for an electric vehicle with harpoon-shift synchronizer." Mechanism and Machine Theory 133 (March 2019): 750–66. http://dx.doi.org/10.1016/j.mechmachtheory.2018.11.018.
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Sun, Xiaomin, Dacheng Feng, Zhengting Cai, and Wensheng Bian. "An ab initio study of the potential energy surfaces for the collision between a Cs atom and an I2 molecule." Canadian Journal of Chemistry 82, no. 7 (July 1, 2004): 1216–22. http://dx.doi.org/10.1139/v04-025.
Повний текст джерелаАнотація:
For the Cs + I2 collision system, a systematic theoretical study is first reported using the ab initio method. Three of eight possible channels are considered. The nonadiabatic coupling between the covalent state and the ionic one is calculated from different angles, especially the T-shape collision. The complete ion-pair formation potential energy surfaces of the T-shape collision in two electronic states (ionic 2B2 state and covalent 2A1 state) and the reactive surface of the linear collision are constructed at the QCISD(T)/SDD level. The main features of potential energy surfaces, such as the minimum energy reaction path, the crossing radius (Rc), and energy minimum geometries, are analyzed. The cross section of this titled system is calculated based on the harpoon mechanism and compared with the available experimental data and those obtained for the M + I2 (M = Li, Na) systems.Key words: ab initio two-state potential energy surfaces, nonadiabatic coupling, ion-pair formation, cross section.
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Law, Che-Leung, Wade Aaron, Rick Austin, Manasi Barath, Evan Callihan, Thomas Evans, Maria Gamez Guerrero, et al. "Preclinical and Nonclinical Characterization of HPN217: A Tri-Specific T Cell Activating Construct (TriTAC) Targeting B Cell Maturation Antigen (BCMA) for the Treatment of Multiple Myeloma." Blood 132, Supplement 1 (November 29, 2018): 3225. http://dx.doi.org/10.1182/blood-2018-99-113921.
Повний текст джерелаАнотація:
Abstract About 31,000 new cases of multiple myeloma (MM) will be diagnosed in the US in 2018. In addition to chemotherapeutic agents, several targeted therapies utilizing distinct mechanisms of action, e.g., proteasome inhibitors (bortezomib, carfilzomib, ixazomib), HDAC inhibitors (panobinostat), Cullin-RING E3 ubiquitin ligase activators (thalidomide, lenalidomide, pomalidomide), and antibodies (daratumumab, elotuzumab) have become available for treating MM. However, MM remains an incurable disease. Patients who relapse after or are refractory to standard of care treatments generally have poor prognosis. In 2018, close to 13,000 patients will die of the disease in the US. Targeting the B cell maturation antigen (BCMA), a BAFF/BLyS and APRIL receptor, for treating MM patients can provide a new treatment approach complementary to existing therapies. CAR-T therapies and an antibody-drug conjugate targeting BCMA have demonstrated early clinical success in the treatment of relapsed refractory MM (RRMM). HPN217 is a tri-specific T cell activating construct (TriTAC) consisting of three binding domains: an N-terminal single domain antibody (sdAb) that binds to human BCMA, a middle sdAb that binds to human serum albumin (HSA), and a C-terminal single chain Fv (scFv) that binds to CD3ε of the T cell receptor (TCR) complex. HPN217 is a highly stable single polypeptide of ~ 53 kDa expressed by CHO cells. Simultaneous engagement of BCMA on a target MM cell and CD3 on a T cell results in T cell activation, functional differentiation and the eventual lysis of the target MM cell. Engineering of an HSA binding domain into HPN217 represents a unique strategy in extending serum half-life, giving the TriTAC molecule a small molecular size and flexibility. This approach is different from Fc-engineering applied in other CD3-based bispecific T cell engaging molecules. The KD of HPN217 binding to recombinant human BCMA, HSA, and recombinant human CD3ε was determined to be 5.5 nM, 6 nM, and 17 nM, respectively, as measured by biolayer interferometry. Flow cytometric analysis on a panel of T cells from normal donors and BCMA positive and BCMA negative tumor cell lines confirmed binding of HPN217 to its native targets expressed on cell surface. The in vitro pharmacological activity of HPN217 was evaluated by T cell-dependent cellular cytotoxicity (TDCC) assays. In co-cultures of T cells from normal human or cynomolgus monkey donors, target tumor cells, and HSA, HPN217 mediated dose-dependent and BCMA-dependent cytotoxicity with EC50 values ranging from 0.05 to 0.7 nM. Killing was dependent on expression of BCMA on target tumor cells. Concomitant with target tumor cell killing, HPN217 also mediated dose-dependent upregulation of CD25 and CD69 on T cells in the TDCC co-cultures when BCMA positive tumor cells were presence. Consistent with the mechanism of action of CD3-based T cell engaging molecules, T cell derived cytokines, e.g., TNFα and IFNγ, were detected. Similar T cell activation could be observed using human or cynomolgus monkey whole blood as a source of T cells. Nonclinical in vivo properties of HPN217 were evaluated in xenograft models and a single dose pharmacokinetic (PK) study in cynomolgus monkeys. HPN217 mediated dose-dependent growth suppression against the RPMI-8226 MM model and Jeko-1 mantle cell lymphoma model expressing relatively low levels of 5,600 and 2,200 copies of BCMA per cell, respectively. In the PK study, a single dose of HPN217 at 0.01, 0.1, or 1 mg/kg was given to cynomolgus monkeys. HPN217 exhibited linear PK behavior over this dose range. Serum half-life was in the range of 64 to 85 hours. Serum half-life, volume of distribution, and clearance appeared to be independent of dose. HPN217 was demonstrated to be stable and remained intact up to 3 weeks in vivo as demonstrated by a functional ligand binding assay using recombinant CD3ε and BCMA, respectively, to capture and detect HPN217. Importantly, serum samples collected one week after dosing were as potent as stock HPN217 in MM tumor cell killing in TDCC assays. Collectively, preclinical and nonclinical characterization suggests that HPN217 is an efficacious novel therapeutic candidate that can provide a convenient dosing schedule for patients. A first-in-human phase 1 clinical trial is planned to evaluate HPN217 in RRMM. Disclosures Law: Harpoon Therapeutics: Employment. Aaron:Harpoon Therapeutics: Employment. Austin:Harpoon Therapeutics: Employment. Barath:Harpoon Therapeutics: Employment. Callihan:Harpoon Therapeutics: Employment. Evans:Harpoon Therapeutics: Employment. Gamez Guerrero:Harpoon Therapeutics: Employment. Hemmati:Harpoon Therapeutics: Employment. Jones:Harpoon Therapeutics: Employment. Kwant:Harpoon Therapeutics: Employment. Lao:Harpoon Therapeutics: Employment. Lemon:Harpoon Therapeutics: Employment. Patnaik:Harpoon Therapeutics: Employment. Sexton:Harpoon Therapeutics: Employment. Wesche:Harpoon Therapeutics: Employment. Xiao:Harpoon Therapeutics: Employment. Yu:Harpoon Therapeutics: Employment. Yu:Harpoon Therapeutics: Employment.
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Liu, Dean-Kuo, King-Chuen Lin, and Jye-Jong Chen. "Reaction dynamics of Mg(4 [sup 1]S[sub 0], 3 [sup 1]D[sub 2]) with H[sub 2]: Harpoon-type mechanism for highly excited states." Journal of Chemical Physics 113, no. 13 (2000): 5302. http://dx.doi.org/10.1063/1.1290125.
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Wang, Defu, Baoxia Wang, Jiangran Wang, Shuting Wang, Weiyu Wang, and Yanbing Niu. "Exogenous Application of Harpin Protein Hpa1 onto Pinellia ternata Induces Systemic Resistance Against Tobacco Mosaic Virus." Phytopathology® 110, no. 6 (June 2020): 1189–98. http://dx.doi.org/10.1094/phyto-12-19-0463-r.
Повний текст джерелаАнотація:
The harpin protein Hpa1 has various beneficial effects in plants, such as promoting plant growth and inducing pathogen resistance. Our previous study found that Hpa1 could significantly alleviate the mosaic symptoms of tobacco mosaic virus (TMV) in Pinellia ternata, indicating that Hpa1 can effectively stimulate resistance. Here, the potential mechanism of disease resistance and field applicability of Hpa1 against TMV in P. ternata were further investigated. The results showed that 15 µg ml−1 Hpa1 had stronger antiviral activity than the control, and its protective effect was better than its curative effect. Furthermore, Hpa1 could significantly induce an increase in defense-related enzyme activity, including polyphenol oxidase, peroxidase, catalase, and superoxide dismutase, as well as increase the expression of disease resistance-related genes (PR1, PR3, PR5, and PDF1.2). Concurrently, Hpa1 significantly increased the content of some disease resistance-related substances, including hydrogen peroxide, phenolics, and callose, whereas the content of malondialdehyde was reduced. In addition, field application analysis demonstrated that Hpa1 could effectively elicit a defense response against TMV in P. ternata. Our findings propose a mechanism by which Hpa1 can prevent TMV infection in Pinellia by inducing systemic resistance, thereby providing an environmentally friendly approach for the use of Hpa1 in large-scale applications to improve TMV resistance in Pinellia.
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Romero-Tamayo, Silvia, Ruben Laplaza, Adrian Velazquez-Campoy, Raquel Villanueva, Milagros Medina та Patricia Ferreira. "W196 and the β-Hairpin Motif Modulate the Redox Switch of Conformation and the Biomolecular Interaction Network of the Apoptosis-Inducing Factor". Oxidative Medicine and Cellular Longevity 2021 (15 січня 2021): 1–19. http://dx.doi.org/10.1155/2021/6673661.
Повний текст джерелаАнотація:
The human apoptosis-inducing factor (hAIF) is a moonlight flavoprotein involved in mitochondrial respiratory complex assembly and caspase-independent programmed cell death. These functions might be modulated by its redox-linked structural transition that enables hAIF to act as a NAD(H/+) redox sensor. Upon reduction with NADH, hAIF undergoes a conformational reorganization in two specific insertions—the flexible regulatory C-loop and the 190-202 β-harpin—promoting protein dimerization and the stabilization of a long-life charge transfer complex (CTC) that modulates its monomer-dimer equilibrium and its protein interaction network in healthy mitochondria. In this regard, here, we investigated the precise function of the β-hairpin in the AIF conformation landscape related to its redox mechanism, by analyzing the role played by W196, a key residue in the interaction of this motif with the regulatory C-loop. Mutations at W196 decrease the compactness and stability of the oxidized hAIF, indicating that the β-hairpin and C-loop coupling contribute to protein stability. Kinetic studies complemented with computational simulations reveal that W196 and the β-hairpin conformation modulate the low efficiency of hAIF as NADH oxidoreductase, contributing to configure its active site in a noncompetent geometry for hydride transfer and to stabilize the CTC state by enhancing the affinity for NAD+. Finally, the β-hairpin motif contributes to define the conformation of AIF’s interaction surfaces with its physiological partners. These findings improve our understanding on the molecular basis of hAIF’s cellular activities, a crucial aspect for clarifying its associated pathological mechanisms and developing new molecular therapies.
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Nugroho, Stevanus K., Neale P. Gibson, Ernst J. W. de Mooij, Chris A. Watson, Hajime Kawahara, and Stephanie Merritt. "Searching for thermal inversion agents in the transmission spectrum of KELT-20b/MASCARA-2b: detection of neutral iron and ionised calcium H&K lines." Monthly Notices of the Royal Astronomical Society 496, no. 1 (June 17, 2020): 504–22. http://dx.doi.org/10.1093/mnras/staa1459.
Повний текст джерелаАнотація:
ABSTRACT We analyse the transmission spectra of KELT-20b/MASCARA-2b to search for possible thermal inversion agents. The data consist of three transits obtained using HARPSN and one using CARMENES. We removed stellar and telluric lines before cross-correlating the residuals with spectroscopic templates produced using a 1D plane-parallel model, assuming an isothermal atmosphere and chemical equilibrium at solar metallicity. Using a likelihood-mapping method, we detect Fe i at > 13σ, Ca ii H$\&$K at > 6σ and confirm the previous detections of Fe ii, Ca ii IR Triplet, and Na i D. The detected signal of Fe i is shifted by −3.4 ± 0.4 km s−1 from the planetary rest frame, which indicates a strong day–night wind. Our likelihood-mapping technique also reveals that the absorption features of the detected species extend to different altitudes in the planet’s atmosphere. Assuming that the line lists are accurate, we do not detect other potential thermal inversion agents (NaH, MgH, AlO, SH, CaO, VO, FeH, and TiO) suggesting that non-chemical equilibrium mechanisms (e.g. a cold-trap) might have removed Ti- and V-bearing species from the upper atmosphere. Our results, therefore, show that KELT-20b/MASCARA-2b cannot possess an inversion layer caused by a TiO/VO-related mechanism. The presence of an inversion layer would therefore likely be caused by metal atoms such as Fe i and Fe ii. Finally, we report a double-peak structure in the Fe i signal in all of our data sets that could be a signature of atmospheric dynamics. However, further investigation is needed to robustly determine the origin of the signal.
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Li, Jun, and Bin Kang. "Dominant species drive seasonal dynamics of the fish community in the Min estuary, China." Oceanological and Hydrobiological Studies 49, no. 1 (March 26, 2020): 34–48. http://dx.doi.org/10.1515/ohs-2020-0004.
Повний текст джерелаАнотація:
AbstractFishery resources are currently facing multiple stresses such as overfishing, pollution and climate change. Looking into processes and mechanisms of the dynamic fish community through detailed quantitative analyses contributes to effective conservation and management of fishery resources. The Min estuary plays an important role in maintaining fisheries in southeastern coastal China, therefore the fish community in the brackish area was investigated and analyzed in this study. A total of 127 species belonging to 91 genera, 49 families and 14 orders were sampled in 2015. Eight indices reflecting four aspects of fish communities were determined, i.e. species richness, species evenness, heterogeneity and taxonomy. Differences between the indices were nonsignificant, suggesting that the use of a single diversity descriptor could not provide a full explanation. Nine dominant species in the Min estuary showed seasonal turnover by rational use of resources and co-occurring species showed correspondingly adequate habitat preferences and feeding habits to avoid competition. The species Harpadon nehereus occurred as the dominant species in three seasons except spring. High values of niche overlap among common or rare species and lower values of niche overlap among all dominant species effectively brought the diversity of the fish community into a state of equilibrium.
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Miao, Weiguo, Xiben Wang, Ming Li, Congfeng Song, Yu Wang, Dongwei Hu, and Jinsheng Wang. "Genetic transformation of cotton with a harpin-encoding gene HpaXoo confers an enhanced defense response against different pathogens through a priming mechanism." BMC Plant Biology 10, no. 1 (2010): 67. http://dx.doi.org/10.1186/1471-2229-10-67.
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Ji, Zhao-Lin, Mei-Hui Yu, Ya-Yan Ding, Jian Li, Feng Zhu, Jun-Xian He, and Li-Na Yang. "Coiled-Coil N21 of Hpa1 in Xanthomonas oryzae pv. oryzae Promotes Plant Growth, Disease Resistance and Drought Tolerance in Non-Hosts via Eliciting HR and Regulation of Multiple Defense Response Genes." International Journal of Molecular Sciences 22, no. 1 (December 28, 2020): 203. http://dx.doi.org/10.3390/ijms22010203.
Повний текст джерелаАнотація:
Acting as a typical harpin protein, Hpa1 of Xanthomonas oryzae pv. oryzae is one of the pathogenic factors in hosts and can elicit hypersensitive responses (HR) in non-hosts. To further explain the underlying mechanisms of its induced resistance, we studied the function of the most stable and shortest three heptads in the N-terminal coiled-coil domain of Hpa1, named N21Hpa1. Proteins isolated from N21-transgenic tobacco elicited HR in Xanthi tobacco, which was consistent with the results using N21 and full-length Hpa1 proteins expressed in Escherichia coli. N21-expressing tobacco plants showed enhanced resistance to tobacco mosaic virus (TMV) and Pectobacterium carotovora subsp. carotovora (Pcc). Spraying of a synthesized N21 peptide solution delayed the disease symptoms caused by Botrytis cinerea and Monilinia fructicola and promoted the growth and drought tolerance of plants. Further analysis indicated that N21 upregulated the expression of multiple plant defense-related genes, such as genes mediated by salicylic acid (SA), jasmonic acid (JA) and ethylene (ET) signaling, and genes related to reactive oxygen species (ROS) biosynthesis. Further, the bioavailability of N21 peptide was better than that of full-length Hpa1Xoo. Our studies support the broad application prospects of N21 peptide as a promising succedaneum to biopesticide Messenger or Illite or other biological pharmaceutical products, and provide a basis for further development of biopesticides using proteins with similar structures.
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Khoza, Thembisile, Ian Dubery, and Lizelle Piater. "Identification of Candidate Ergosterol-Responsive Proteins Associated with the Plasma Membrane of Arabidopsis thaliana." International Journal of Molecular Sciences 20, no. 6 (March 14, 2019): 1302. http://dx.doi.org/10.3390/ijms20061302.
Повний текст джерелаАнотація:
The impact of fungal diseases on crop production negatively reflects on sustainable food production and overall economic health. Ergosterol is the major sterol component in fungal membranes and regarded as a general elicitor or microbe-associated molecular pattern (MAMP) molecule. Although plant responses to ergosterol have been reported, the perception mechanism is still unknown. Here, Arabidopsis thaliana protein fractions were used to identify those differentially regulated following ergosterol treatment; additionally, they were subjected to affinity-based chromatography enrichment strategies to capture and categorize ergosterol-interacting candidate proteins using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Mature plants were treated with 250 nM ergosterol over a 24 h period, and plasma membrane-associated fractions were isolated. In addition, ergosterol was immobilized on two different affinity-based systems to capture interacting proteins/complexes. This resulted in the identification of defense-related proteins such as chitin elicitor receptor kinase (CERK), non-race specific disease resistance/harpin-induced (NDR1/HIN1)-like protein, Ras-related proteins, aquaporins, remorin protein, leucine-rich repeat (LRR)- receptor like kinases (RLKs), G-type lectin S-receptor-like serine/threonine-protein kinase (GsSRK), and glycosylphosphatidylinositol (GPI)-anchored protein. Furthermore, the results elucidated unknown signaling responses to this MAMP, including endocytosis, and other similarities to those previously reported for bacterial flagellin, lipopolysaccharides, and fungal chitin.
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Fellin, Tommaso, Siro Luvisetto, Michele Spagnolo, and Daniela Pietrobon. "Modal Gating of Human CaV2.1 (P/Q-type) Calcium Channels." Journal of General Physiology 124, no. 5 (October 25, 2004): 463–74. http://dx.doi.org/10.1085/jgp.200409035.
Повний текст джерелаАнотація:
The single channel gating properties of human CaV2.1 (P/Q-type) calcium channels were investigated with cell-attached patch-clamp recordings on HEK293 cells stably expressing these calcium channels. Human CaV2.1 channels showed a complex modal gating, which is described in this and the preceding paper (Luvisetto, S., T. Fellin, M. Spagnolo, B. Hivert, P.F. Brust, M.M. Harpold, K.A. Stauderman, M.E. Williams, and D. Pietrobon. 2004. J. Gen. Physiol. 124:445–461). Here, we report the characterization of the so-called b gating mode. A CaV2.1 channel in the b gating mode shows a bell-shaped voltage dependence of the open probability, and a characteristic low open probability at high positive voltages, that decreases with increasing voltage, as a consequence of both shorter mean open time and longer mean closed time. Reversible transitions of single human CaV2.1 channels between the b gating mode and the mode of gating in which the channel shows the usual voltage dependence of the open probability (nb gating mode) were much more frequent (time scale of seconds) than those between the slow and fast gating modes (time scale of minutes; Luvisetto et al., 2004), and occurred independently of whether the channel was in the fast or slow mode. We show that the b gating mode produces reversible uncoupling of inactivation in human CaV2.1 channels. In fact, a CaV2.1 channel in the b gating mode does not inactivate during long pulses at high positive voltages, where the same channel in both fast-nb and slow-nb gating modes inactivates relatively rapidly. Moreover, a CaV2.1 channel in the b gating mode shows a larger availability to open than in the nb gating modes. Regulation of the complex modal gating of human CaV2.1 channels could be a potent and versatile mechanism for the modulation of synaptic strength and plasticity as well as of neuronal excitability and other postsynaptic Ca2+-dependent processes.
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McCool, Brian A., Jean-Phillipe Pin, Michael M. Harpold, Paul F. Brust, KENNETH A. Stauderman, and David M. Lovinger. "Rat group I Metabotropic Glutamate Receptors Inhibit Neuronal Ca2+ Channels via Multiple Signal Transduction Pathways in HEK 293 Cells." Journal of Neurophysiology 79, no. 1 (January 1, 1998): 379–91. http://dx.doi.org/10.1152/jn.1998.79.1.379.
Повний текст джерелаАнотація:
McCool, Brian A., Jean-Phillipe Pin, Michael M. Harpold, Paul F. Brust, Kenneth A. Stauderman, and David M. Lovinger. Rat group I metabotropic glutamate receptors inhibit neuronal Ca2+ channels via multiple signal transduction pathways in HEK 293 cells. J. Neurophysiol. 79: 379–391, 1998. We have shown previously that metabotropic glutamate receptors with group I-like pharmacology couple to N-type and P/Q-type calcium channels in acutely isolated cortical neurons using G proteins most likely belonging to the Gi/Go subclass. To better understand the potential mechanisms forming the basis for group I mGluR modulation of voltage-gated calcium channels in the CNS, we have examined the ability of specific mGluRs to couple to neuronal N-type (α1B-1/α2δ/β1b) and P/Q-type (α1A-2/α2δ/β1b) voltage-gated calcium channels in an HEK 293 heterologous expression system. Using the whole cell patch-clamp technique where intracellular calcium is buffered to low levels, we have shown that group I receptors inhibit both N-type and P/Q-type calcium channels in a voltage-dependent fashion. Similar to our observations in cortical neurons, this voltage-dependent inhibition is mediated almost entirely by N-ethylmaleimide (NEM)-sensitive heterotrimeric G proteins, strongly suggesting that these receptors can use Gi/Go-like G proteins to couple to N-type and P/Q-type calcium channels. However, inconsistent with the apparent NEM sensitivity of group I modulation of calcium channels, modulation of N-type channels in group I mGluR-expressing cells was only partially sensitive to pertussis toxin (PTX), indicating the potential involvement of both PTX-sensitive and -resistant G proteins. The PTX-resistant modulation was voltage dependent and entirely resistant to NEM and cholera toxin. A time course of treatment with PTX revealed that this toxin caused group I receptors to slowly shift from using a primarily NEM-sensitive G protein to using a NEM-resistant form. The PTX-induced switch from NEM-sensitive to -resistant modulation was also dependent on protein synthesis, indicating some reliance on active cellular processes. In addition to these voltage-dependent pathways, perforated patch recordings on group I mGluR-expressing cells indicate that another slowly developing, calcium-dependent form of modulation for N-type channels may be seen when intracellular calcium is not highly buffered. We conclude that group I mGluRs can modulate neuronal Ca2+ channels using a variety of signal transduction pathways and propose that the relative contributions of different pathways may exemplify the diversity of responses mediated by these receptors in the CNS.
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Schade, Henning, Sumit Madan, Eva Medvedova, Rajneesh Nath, Lisa Knapp, Bryan Lemon, and Liping Laura Sun. "HPN217-3001: A Phase 1/2 Open-Label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN217, a Bcma-Targeting T-Cell Engager, in Patients with Relapsed/Refractory Multiple Myeloma." Blood 136, Supplement 1 (November 5, 2020): 10. http://dx.doi.org/10.1182/blood-2020-136012.
Повний текст джерелаАнотація:
Background B cell maturation antigen (BCMA) has emerged as a promising target for multiple myeloma (MM) therapies based on its restricted expression profile and functional role in promoting MM cell survival. Some of these BCMA targeting molecules, including CAR-T cells and CD3-based T cell engaging molecules, have demonstrated efficacy against relapsed/refractory MM (R/R MM) in clinical trials. HPN217 is a BCMA -targeting T cell engager with Harpoon's proprietary Tri-specific T cell Activating Construct (TriTAC®) platform, a recombinant polypeptide of ~50kDa containing three humanized antibody-derived binding domains, targeting BCMA (for tumor binding), albumin (for half-life extension) and CD3 (for T cell engagement). It has been engineered to be a small, globular protein to enable efficient exposure in tumor tissue with prolonged half-life and excellent stability under physiological conditions. HPN217 mediates potent target tumor cell killing in a BCMA-specific manner in vitro and in xenograft models in the presence of T cells. Consistent with its mechanism of action (MOA), tumor cell killing is accompanied by T cell activation, cytokine induction, and T cell expansion. HPN217 binds monomerically to CD3 and BCMA, minimizing non-specific T-cell activation. Study Design and Methods HPN217-3001 is an ongoing Phase 1/2, open-label, multicenter, global study of the safety, tolerability, and pharmacokinetics of HPN217 in patients with relapsed and refractory multiple myeloma. The study is divided into 2 parts: Dose Escalation (Part 1) and Expansion (Part 2). Part 1 of the study will determine the Maximum Tolerated Dose (MTD) or the recommended Phase 2 dose (RP2D); Part 2 of the trial will evaluate the safety and efficacy of HPN217 at MTD/RP2D in patients with R/R MM. Patients, who have received at least 3 prior therapies (including proteasome inhibitor, immune modulatory drug, and an anti-CD38 antibody each) and are not candidates for or intolerant to all therapies known to provide clinical benefit in MM, are eligible for enrollment. Prior exposure to a BCMA-targeting agent is permitted in Part 1 but not in Part 2. HPN217 is administered once weekly via IV infusion on Days 1, 8 and 15 during each 21-day cycle at a flat dose. Dose escalation is being performed in serial patient cohorts starting with single patient dose cohorts followed by a conventional 3 + 3 design. Intra-patient dose escalation is permitted. Dose expansion will be initiated once the MTD or a RP2D is established based on safety, preliminary efficacy, PK, and pharmacodynamic data from dose escalation, with a Simon 2-stage design to assess preliminary clinical efficacy of HPN217. Patients may continue weekly HPN217 treatment until disease progression. Primary study endpoints include frequency and severity of treatment-emergent AEs (TEAEs) graded according to NCI CTCAE version 5.0, number and severity of dose limiting toxicities (DLTs) following treatment with HPN217, and PK parameters of HPN217. The study will also evaluate overall response rate (ORR) based on IMWG response criteria, progression-free survival (PFS) and overall survival (OS), duration of response (DOR), immunogenicity of HPN217, and other exploratory endpoints related to the mechanism of action of HPN217. (NCT04184050) Disclosures Madan: Sanofi: Other: Ad hoc advisory board; GSK: Other: Ad hoc advisory board, Speakers Bureau; Karopharm: Speakers Bureau; Amgen: Other: Ad hoc advisory board, Speakers Bureau; Janssen: Other: Ad hoc advisory board, Speakers Bureau; Takeda: Other: Ad hoc advisory board, Speakers Bureau; Celgene/BMS: Other: Ad hoc advisory board, Speakers Bureau. Nath:Harpoon Therapeutics: Consultancy. Knapp:Harpoon Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lemon:Harpoon Therapeutics: Current Employment, Current equity holder in publicly-traded company. Sun:Harpoon Therapeutics: Current Employment, Current equity holder in publicly-traded company.
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Nakata, Masanobu, and Bernd Kreikemeyer. "Genetics, Structure, and Function of Group A Streptococcal Pili." Frontiers in Microbiology 12 (February 9, 2021). http://dx.doi.org/10.3389/fmicb.2021.616508.
Повний текст джерелаАнотація:
Streptococcus pyogenes (Group A Streptococcus; GAS) is an exclusively human pathogen. This bacterial species is responsible for a large variety of infections, ranging from purulent but mostly self-limiting oropharynx/skin diseases to streptococcal sequelae, including glomerulonephritis and rheumatic fever, as well as life-threatening streptococcal toxic-shock syndrome. GAS displays a wide array of surface proteins, with antigenicity of the M protein and pili utilized for M- and T-serotyping, respectively. Since the discovery of GAS pili in 2005, their genetic features, including regulation of expression, and structural features, including assembly mechanisms and protein conformation, as well as their functional role in GAS pathogenesis have been intensively examined. Moreover, their potential as vaccine antigens has been studied in detail. Pilus biogenesis-related genes are located in a discrete section of the GAS genome encoding fibronectin and collagen binding proteins and trypsin-resistant antigens (FCT region). Based on the heterogeneity of genetic composition and DNA sequences, this region is currently classified into nine distinguishable forms. Pili and fibronectin-binding proteins encoded in the FCT region are known to be correlated with infection sites, such as the skin and throat, possibly contributing to tissue tropism. As also found for pili of other Gram-positive bacterial pathogens, GAS pilin proteins polymerize via isopeptide bonds, while intramolecular isopeptide bonds present in the pilin provide increased resistance to degradation by proteases. As supported by findings showing that the main subunit is primarily responsible for T-serotyping antigenicity, pilus functions and gene expression modes are divergent. GAS pili serve as adhesins for tonsillar tissues and keratinocyte cell lines. Of note, a minor subunit is considered to have a harpoon function by which covalent thioester bonds with host ligands are formed. Additionally, GAS pili participate in biofilm formation and evasion of the immune system in a serotype/strain-specific manner. These multiple functions highlight crucial roles of pili during the onset of GAS infection. This review summarizes the current state of the art regarding GAS pili, including a new mode of host-GAS interaction mediated by pili, along with insights into pilus expression in terms of tissue tropism.
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Liu, Yue, Xiaoyun Zhou, Wenbo Liu, Jiamin Huang, Qinghuan Liu, Jianzhang Sun, Xinfeng Cai, and Weiguo Miao. "HpaXpm, a novel harpin of Xanthomonas phaseoli pv. manihotis, acts as an elicitor with high thermal stability, reduces disease, and promotes plant growth." BMC Microbiology 20, no. 1 (January 6, 2020). http://dx.doi.org/10.1186/s12866-019-1691-4.
Повний текст джерелаАнотація:
Abstract Background Harpins are proteins secreted by the type III secretion system of Gram-negative bacteria during pathogen–plant interactions that can act as elicitors, stimulating defense and plant growth in many types of non-host plants. Harpin-treated plants have higher resistance, quality and yields and, therefore, harpin proteins may potentially have many valuable agricultural applications. Harpins are characterized by high thermal stability at 100 °C. However, it is unknown whether harpins are still active at temperatures above 100 °C or whether different temperatures affect the activity of the harpin protein in different ways. The mechanism responsible for the heat stability of harpins is also unknown. Results We identified a novel harpin, HpaXpm, from the cassava blight bacteria Xanthomonas phaseoli pv. manihotis HNHK. The predicted secondary structure and 3-D structure indicated that the HpaXpm protein has two β-strand domains and two major α-helical domains located at the N- and C-terminal regions, respectively. A phylogenetic tree generated using the maximum likelihood method grouped HpaXpm in clade I of the Hpa1 group along with harpins produced by other Xanthomonas spp. (i.e., HpaG-Xag, HpaG-Xcm, Hpa1-Xac, and Hpa1Xm). Phenotypic assays showed that HpaXpm induced the hypersensitive response (HR), defense responses, and growth promotion in non-host plants more effectively than Hp1Xoo (X. oryzae pv. oryzae). Quantitative real-time PCR analysis indicated that HpaXpm proteins subjected to heat treatments at 100 °C, 150 °C, or 200 °C were still able to stimulate the expression of function-related genes (i.e., the HR marker genes Hin1 and Hsr203J, the defense-related gene NPR1, and the plant growth enhancement-related gene NtEXP6); however, the ability of heat-treated HpaXpm to induce HR was different at different temperatures. Conclusions These findings add a new member to the harpin family. HpaXpm is heat-stable up to 200 °C and is able to stimulate powerful beneficial biological functions that could potentially be more valuable for agricultural applications than those stimulated by Hpa1Xoo. We hypothesize that the extreme heat resistance of HpaXpm is because the structure of harpin is very stable and, therefore, the HpaXpm structure is less affected by temperature.
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Liu, Yue, Xiaoyun Zhou, Wenbo Liu, and Weiguo Miao. "The stability of the coiled-coil structure near to N-terminus influence the heat resistance of harpin proteins from Xanthomonas." BMC Microbiology 20, no. 1 (November 12, 2020). http://dx.doi.org/10.1186/s12866-020-02029-6.
Повний текст джерелаАнотація:
Abstract Background Heat resistance is a common characteristic of harpins, a class of proteins found in Gram-negative bacteria, which may be related to the stability of coiled-coil (CC) structure. The CC structure is a ubiquitous protein folding and assembly motif made of α-helices wrapping around each other forming a supercoil. Specifically, whether the stability of the CC structure near to N-terminus of four selected harpin proteins from Xanthomonas (hereafter referred to as Hpa1) would influence their characteristics of heat resistance was investigated. We used bioinformatics approach to predict the structure of Hpa1, used the performance of hypersensitive response (HR)-induction activity of Hpa1 and circular dichroism (CD) spectral analyses to detect the relationship between the stability of the CC structure of Hpa1 and heat resistance. Results Each of four-selected Hpa1 has two α-helical regions with one in their N-terminus that could form CC structure, and the other in their C-terminus that could not. And the important amino acid residues involved in the CC motifs are located on helices present on the surface of these proteins, indicating they may engage in the formation of oligo mericaggregates, which may be responsible for HR elicitation by harpins and their high thermal stability. Increased or decreased the probability of forming a CC could either induce a stronger HR response or eliminate the ability to induce HR in tobacco after high temperature treatment. In addition, although the four Hpa1 mutants had little effect on the induction of HR by Hpa1, its thermal stability was significantly decreased. The α-helical content increased with increasing temperature, and the secondary structures of Hpa1 became almost entirely α-helices when the temperature reached 200 °C. Moreover, the stability of the CC structure near to N-terminus was found to be positively correlated with the heat resistance of Hpa1. Conclusions The stability of the CC structure might sever as an inner drive for mediating the heat resistance of harpin proteins. Our results offer a new insight into the interpretation of the mechanism involved in the heat resistance of harpin protein and provide a theoretical basis for further harpin function investigations and structure modifications.
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Huang, Maoxi, Yunlong Yan, Li Wang, Jun Chen, Tao Liu, Xin Xie та Xiangyang Li. "Research on the Interaction Mechanism Between α Mino-Phosphonate Derivative Q-R and Harpin-Binding Protein 1 in Tobacco (Nicotiana tabacum) Plants". Frontiers in Microbiology 12 (23 березня 2021). http://dx.doi.org/10.3389/fmicb.2021.621875.
Повний текст джерелаАнотація:
Amino-phosphonate derivative R-diphenyl-1-(4-methylbenzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-R) has a high protective anti-tobacco mosaic virus (TMV) activity. However, the mechanism responsible for Q-R’s effect on TMV infection is largely unknown. Here, we studied the expression levels of harpin-binding protein 1 (HrBP1) and pathogenesis-related protein-1a (PR-1a) in TMV-infected tobacco plants by using reverse transcription quantitative real-time PCR. Then, we verified the interactions between Q-R and the HrBP1 protein from Escherichia coli using isothermal titration calorimetry and studied the Q-R-associated assembly of HrBP1 using size-exclusion chromatography. The results showed that the expression levels of HrBP1 and PR-1a genes were significantly increased by Q-R at the transcriptional level in TMV-infected tobacco plants, and the E. coli-expressed HrBP1 protein was assembled into oligomers by Q-R via binding to HrBP1 with a dissociation constant of 1.19 μM. We, therefore, concluded that Q-R activated the HrBP1 and PR-1a genes and enhanced the ability of HrBP1 to assemble in tobacco plants.
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Wei, Li, Ya Peng, Naiyuan Shao та Peng Zhou. "Downregulation of Tim-1 inhibits the proliferation, migration and invasion of glioblastoma cells via the miR-133a/TGFBR1 axis and the restriction of Wnt/β-catenin pathway". Cancer Cell International 21, № 1 (5 липня 2021). http://dx.doi.org/10.1186/s12935-021-02036-1.
Повний текст джерелаАнотація:
Abstract Background Glioblastoma remains one of the most lethal brain cancers. T-cell immunoglobulin and mucin domain 1 (Tim-1) is associated with various immune diseases. The molecular mechanism of Tim-1 in regulating glioblastoma cell proliferation, invasion, and migration is still unknown. Moreover, it has shown that miR-133a plays an important role in glioblastoma. However, little is known about the interaction between Tim-1 and miR-133a in glioblastoma. Methods Tim-1 expression in glioblastoma and normal brain tissues was detected by qPCR, Western Blot and IHC. After Tim-1 knockdown in U251 and U87 cells, genes showing significantly differential expression, along with the significant differential miRNAs were analyzed using RNA-seq analysis. The binding sites were verified using dual-luciferase reporter gene assay. U251 and U87 cells were allocated into the small harpin-negative control (sh-NC), sh-Tim-1, sh-Tim-1 + inhibitor NC, and sh-Tim-1 + miR-133a inhibitor group. Cell proliferation, migration, and invasion were determined by CCK-8, flow cytometry, wound-healing and Transwell assays, respectively. Next, U251 and U87 cells were allocated into the mimic NC, miR-133a mimic, miR-133a mimic + pcDNA3.1, and miR-133a mimic + pcDNA3.1-TGFBR1 groups, followed by the detection of cell proliferation, migration, and invasion. Western blot was used to identify the expression of vital kinases in the Wnt/β-catenin pathway. Results Tim-1 was highly expressed in glioblastoma tissues compared with that in normal brain tissues. RNA-seq analysis showed that Tim-1 knockdown could lead to the downregulation of TGFBR1 and the upregulation of miR-133a. The binding sites between TGFBR1 and miR-133a were confirmed. Tim-1 knockdown impaired the invasion, migration, proliferation of U251 and U87 cells, which could be reversed by miR-133a downregulation. miR-133a upregulation inhibited the proliferation, invasion, and migration of U251 and U87 cells, which could be reversed by TGFBR1 upregulation. Tim-1 knockdown and miR-133a upregulation could inhibit the activation of the Wnt/β-catenin pathway, while the elevation of TGFBR1 showed opposite effects. Conclusion Tim-1 knockdown inhibited glioblastoma cell proliferation, invasion, and migration through the miR-133a/TGFBR1 axis and restrained the activation of the Wnt/β-catenin pathway.